Triethyloxonium tetrafluoroborate → [(R)-2-Benzyloxy-1-(6-fluoro-1-pyridin-2-yl-1H-benzoimidazol-2-yl)ethyl]carbamic acid tert-butyl ester

HRID 243015

反応式

HRID 243015 の反応式
[C:1]([O:5][C:6](=[O:21])[NH:7][C@H:8]([C:18](=O)[NH2:19])[CH2:9][O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)([CH3:4])([CH3:3])[CH3:2].F[B-](F)(F)F.C([O+](CC)CC)C.[F:34][C:35]1[CH:36]=[C:37]([NH:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][N:44]=2)[C:38](N)=[CH:39][CH:40]=1>C1COCC1>[C:1]([O:5][C:6](=[O:21])[NH:7][C@H:8]([C:18]1[N:42]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][N:44]=2)[C:37]2[CH:36]=[C:35]([F:34])[CH:40]=[CH:39][C:38]=2[N:19]=1)[CH2:9][O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)([CH3:4])([CH3:3])[CH3:2]

参加物

5

反応物 3

HCID 2723982Triethyloxonium tetrafluoroborateHCID 7216900((S)-2-Benzyloxy-1-carbamoylethyl)carbamic acid tert-butyl esterHCID 681571794-Fluoro-N2-pyridin-2-ylbenzene-1,2-diamine

生成物 1

HCID 68157510[(R)-2-Benzyloxy-1-(6-fluoro-1-pyridin-2-yl-1H-benzoimidazol-2-yl)ethyl]carbamic acid tert-butyl ester収率 53.4%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of ((S)-2-benzyloxy-1-carbamoylethyl)carbamic acid tert-butyl ester (820 mg, 2.8 mmol) in anhydrous THF (10 mL) was added triethyloxonium tetrafluoroborate (550 mg, 2.9 mmol) in one portion under a nitrogen atmosphere. The resulting mixture was stirred at RT for 2 h. The volatiles were removed in vacuo and the resulting residue redissolved in absolute EtOH (10 mL). To the mixture was added 4-fluoro-N2-pyridin-2-yl-benzene-1,2-diamine (355 mg, 1.7 mmol) and the mixture stirred at 75° C. for 16 h. The volatiles were removed in vacuo and the resulting residue partitioned between DCM and a saturated aqueous solution of NaHCO3. The aqueous phase was further extracted with DCM and the combined organic fractions washed with water, dried (MgSO4) and concentrated in vacuo. The resulting residue purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in cHex) to afford the title compound as a yellow oil (420 mg, 53%). LCMS (Method B): RT 3.95 min [M+H]+ 463.1.

後処理

  1. customThe volatiles were removed in vacuo
  2. dissolutionthe resulting residue redissolved in absolute EtOH (10 mL)
  3. stirringthe mixture stirred at 75° C. for 16 h
  4. customThe volatiles were removed in vacuo
  5. customthe resulting residue partitioned between DCM
  6. extractionThe aqueous phase was further extracted with DCM
  7. washthe combined organic fractions washed with water
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customThe resulting residue purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in cHex)

出典と根拠

ORDレコード
ord-deb2e041a84e4f4eacd05e15f66ce7cf
出典データセット
uspto-grants-2014_02
特許番号
US08653089B2

関連ノート

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